Light, particularly the sunburn spectrum (UVB, 280-320 nm), has been implicated as an etiologic agent in the induction of skin tumors in animals and man. We have shown that the administration of carotenoid pigments to patients with erythropoietic protoporphyria can ameliorate the light sensitivity associated with this disease, and that the administration of these pigments to normal volunteers was found to have slight but statistically significant action in delaying the appearance of erythema caused by the sunburn range. We have also found that phytoene, a precursor pigment having absorption maxima in the sunburn range, significantly decreased the erythemal reaction in guinea pigs exposed to this radiation. In addition, we and others have shown that carotenoid pigments can inhibit the formation of free radicals which have been implicated in photocarcinogenesis. Therefore we have studied the effect of the systemic administration of several carotenoid pigments on the development of skin tumors induced by sunburn radiation and topical carcinogens in hairless mice. We have found that the administration of beta-carotene, phytoene or canthaxanthin causes a delay in development, and inhibits significantly the development of tumors induced by UV-B (290-320 nm) per mouse, in hairless mice receiving these pigments. In addition, beta-carotene has an inhibitory effect on dimethyl benz (a)anthracene-induced tumors, but phytoene and canthaxanthin have no such effect. We now propose to extend our studies in two directions; 1) to investigate the possible mechanisms of action of carotenoid protection, by determining photo-product formation on DNA and cellular damage in animals receiving each of the pigments as compared to animals receiving placebo, and to study some aspects of the pharmacokinetics of these pigments, either alone or in combination, to establish the most effective administration methods for maximal tumor inhibitory effect. In addition, we plan to study the effect of crystalline preparations of the water soluble carotenoid, crocetin and other carotenoids as they become available, on the effect of UV as well as chemically-induced skin tumors.